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The Role of APOBEC3 A/G-induced RNA Editing in Stress Response of Immune Cells.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of APOBEC3 A/G-induced RNA Editing in Stress Response of Immune Cells./
作者:	Alqassim, Emad Y.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	96 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Contained By:	Dissertations Abstracts International81-04B.
標題:	Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13857714
ISBN:	9781088365168

The Role of APOBEC3 A/G-induced RNA Editing in Stress Response of Immune Cells.
Alqassim, Emad Y.

The Role of APOBEC3 A/G-induced RNA Editing in Stress Response of Immune Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 96 p.

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

Thesis (Ph.D.)--State University of New York at Buffalo, 2019.

This item must not be sold to any third party vendors.

Project 1: Macrophages acquire proinflammatory M1 phenotype in response to microbial products or proinflammatory cytokines such as IFN-g, TNF and TLR ligands. However, intracellular mechanisms mediating M1 polarization are incompletely understood. We recently described identification APOBEC3A-mediated cellular site-specific C-to-U RNA editing in M1 macrophages. However, the functional significance of this RNA editing is uncertain. Here, we show that RNA editing in macrophages is also induced by viral infections including adenovirus, influenza, and Maraba viruses. Knockdown (KD) of A3A impairs cellular RNA editing and alters M1-related gene expression and cytokine secretion patterns. RNA-Seq analysis shows that A3A causes protein recoding RNA editing in dozens of genes, including novel highly edited (>50%) genes THOC5 and ZNF124A during M1 polarization. A3A KD reduces expression of IL6, IL23A, IL12B genes, surface protein expression of CD86 and the secretion of proinflammatory cytokines IL-1b and TNFa in M1 macrophages. KD of A3A increases glycolysis and glycolytic capacity. These results demonstrate that induction of RNA editing by A3A is required for optimum polarization of proinflammatory macrophages and that epitranscriptomic enzymatic recoding plays a role in macrophage phenotype plasticity.Project 2:Background: Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes and macrophages in response to hypoxia and interferons, the physiological significance of such editing is unclear.Results: Here, we show that the related cytidine deaminase, APOBEC3G, induces site-specific C-to-U RNA editing in natural killer cells, lymphoma cell lines, and, to a lesser extent, CD8-positive T cells upon cellular crowding and hypoxia. In contrast to expectations from its anti-HIV-1 function, the highest expression of APOBEC3G is shown to be in cytotoxic lymphocytes. RNA-seq analysis of natural killer cells subjected to cellular crowding and hypoxia reveals widespread Cto- U mRNA editing that is enriched for genes involved in mRNA translation and ribosome function. APOBEC3G promotes Warburg-like metabolic remodeling in HuT78 T cells under similar conditions. Hypoxia-induced RNA editing by APOBEC3G can be mimicked by the inhibition of mitochondrial respiration and occurs independently of HIF-1α.Conclusions: APOBEC3G is an endogenous RNA editing enzyme in primary natural killer cells and lymphoma cell lines. This RNA editing is induced by cellular crowding and mitochondrial respiratory inhibition to promote adaptation to hypoxic stress.

ISBN: 9781088365168Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

APOBEC3

The Role of APOBEC3 A/G-induced RNA Editing in Stress Response of Immune Cells.
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